METHYLGLYOXAL-DERIVED MODIFICATIONS IN LENS AGING AND CATARACT FORMATION

PURPOSE. To determine whether the Maillard reaction of methylglyoxal i s associated with human lens aging and cataractogenesis and to investi gate how glutathione depletion affects methylglyoxal-derived modificat ions in organ-cultured lenses. METHODS. Antibodies against methylglyox al-derived modifications were developed in rabbits and purified by imm unoaffinity chromatography. A competitive enzyme-linked immunosorbent assay (ELISA) measured methylglyoxal-derived products in human lens pr oteins. Lenses of galactosemic rats grown in organ culture were used t o assess the role of glutathione-dependent pathways in methylglyoxal m etabolism and Maillard reactions. RESULTS. Methylglyoxal-derived modif ications in the human lens were age dependent, and brunescent lenses h ad the highest levels of these modifications. Immunofluorescence stain ing identified antigens distributed throughout the lens, with higher l evels in old lenses than in younger ones. Experiments with normal or g alactosemic rat lenses grown in organ culture showed that lens protein s do not have an increase in methylglyoxal-modified proteins when cult ured in medium containing 500 mu M methylglyoxal alone, but they accum ulate modified proteins when cultured with DL-glyceraldehyde. Inclusio n of 30 mM glucose in the medium marginally increased methyl glyoxal-d erived products, but there was no correlation between lens glutathione content and methyglyoxal-derived modifications. CONCLUSIONS. Methylgl yoxal-mediated Maillard reactions that occur in the human lens may pla y a role in lens aging and cataract formation. Methylglyoxal is probab ly derived from metabolic pathways within the lens. Decreased glutathi one in organ-cultured rat lenses does not significantly influence meth ylglyoxal-mediated Maillard reactions.